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This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Jia-Yuan Zhuang, Zhi-Yao Chen, Tao Zhang, Du-Peng Tang, Xiao-Yin Jiang, Ze-Hao Zhuang. Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis. Med Sci Monit, 2017; 23: 542-547. DOI: 10.12659/MSM.898131.
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AIMS: The aims of this study are to apply a theory-based mechanistic model to describe the pharmacokinetics (PK) and pharmacodynamics (PD) of S- and R-warfarin. METHODS: Clinical data were obtained from 264 patients. Total concentrations for S- and R-warfarin were measured by ultra-high performance liquid tandem mass spectrometry. Genotypes were measured using pyrosequencing. A sequential population PK parameter with data method was used to describe the international normalized ratio (INR) time course. Data were analyzed with NONMEM. Model evaluation was based on parameter plausibility and prediction-corrected visual predictive checks. RESULTS: Warfarin PK was described using a one-compartment model. CYP2C9 *1/*3 genotype had reduced clearance for S-warfarin, but increased clearance for R-warfarin. The in vitro parameters for the relationship between prothrombin complex activity (PCA) and INR were markedly different (A = 0.560, B = 0.386) from the theory-based values (A = 1, B = 0). There was a small difference between healthy subjects and patients. A sigmoid Emax PD model inhibiting PCA synthesis as a function of S-warfarin concentration predicted INR. Small R-warfarin effects was described by competitive antagonism of S-warfarin inhibition. Patients with VKORC1 AA and CYP4F2 CC or CT genotypes had lower C50 for S-warfarin. CONCLUSION: A theory-based PKPD model describes warfarin concentrations and clinical response. Expected PK and PD genotype effects were confirmed. The role of predicted fat free mass with theory-based allometric scaling of PK parameters was identified. R-warfarin had a minor effect compared with S-warfarin on PCA synthesis. INR is predictable from 1/PCA in vivo.
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Anticoagulantes/administración & dosificación , Procedimientos Quirúrgicos Cardíacos/métodos , Modelos Biológicos , Warfarina/administración & dosificación , Adolescente , Adulto , Anciano , Anticoagulantes/farmacocinética , Anticoagulantes/farmacología , Composición Corporal/fisiología , Tamaño Corporal/fisiología , Cromatografía Líquida de Alta Presión , Familia 4 del Citocromo P450/genética , Femenino , Genotipo , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Dinámicas no Lineales , Estereoisomerismo , Espectrometría de Masas en Tándem , Vitamina K Epóxido Reductasas/genética , Warfarina/farmacocinética , Warfarina/farmacología , Adulto JovenRESUMEN
BACKGROUND We designed this study to investigate the influence of different ratios of n-6/n-3 polyunsaturated fatty acid in the diet of reflux esophagitis (RE) rats' and the effect on the PI3K/Akt pathway. MATERIAL AND METHODS RE rats were randomly divided into a sham group and modeling groups of different concentrations of n-6/n-3 polyunsaturated fatty acid (PUFA): 12:1 group, 10:1 group, 5:1 group, and 1:1 group. RT-PCR and Western-blot were used to detect the expression of PI3K, Akt, p-Akt, NF-κBp50, and NF-κBp65 proteins in esophageal tissue. RESULTS In the n-6/n-3 PUFAs groups the expression of PI3K, Akt, p-Akt, nf-κbp50, and NF-κBp65 mRNA decreased with the decrease in n-6/n-3 ratios in the diet. The lowest expression of each indicator occurred in the 1:1 n-6/n-3 group compared with other n-6/n-3 groups, the difference was statistically significant (p<0.05). CONCLUSIONS The inhibition of n-3 PUFAs in the development of esophageal inflammation in rats with RE was attributed to the function of PI3K/Akt-NF-κB signaling pathway.
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Esofagitis Péptica/dietoterapia , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Dieta , Esofagitis Péptica/metabolismo , Masculino , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/biosíntesis , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Two kinds of soy sauces were prepared with Aspergillus oryzae koji (SSAO) and mixed koji (SSAOM, A. oryzae mouldstarter:Monascus purpureus mouldstarter = 1:2, w/w) respectively. The effects of mixed koji on the essential indices, oxygen radical absorption capacity, color indices, free amino acids and volatile compounds of soy sauce have been studied, followed by a sensory evaluation between SSAO and SSAOM. RESULTS: The contents of non-salt soluble solid, reducing sugar, total acid, total nitrogen and amino nitrogen in SSAOM increased by 21.50%, 9.88%, 15.35%, 5.98% and 41.43%, respectively, compared with the control SSAO, owing to the higher activities of acid protease and glucoamylase in the mixed koji. Moreover, SSAOM showed higher antioxidant activity, higher levels of free amino acids and much more attractive color. Meanwhile, flavor groups such as esters, aldehydes, pyrazines and sulfur-containing compounds in SSAOM were also improved. The contents of free amino acids and aroma compounds were consistent with the sensory evaluation. According to descriptive sensory analysis, SSAOM showed higher intensity for sweet and umami attributes; in addition, higher flowery, burnt, fruity and caramel-like attributes were perceived in SSAOM, while SSAO showed higher ethanolic and sour attributes. CONCLUSIONS: The investigated soy sauce prepared with mixed koji can be considered as an effective method to accelerate the fermentation process and improve the flavor of soy sauce.
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Aspergillus oryzae/fisiología , Manipulación de Alimentos/métodos , Monascus/fisiología , Alimentos de Soja/análisis , China , Fermentación , GustoRESUMEN
This study investigates the optical design of planar curved LED end-lit light bars using v cuts as light-diverting structures. The application of LEDs in automotive lighting has become popular, especially in signal lamps and daytime running lamps. Most designs adopt a direct back light using arrays of LEDs with diffusive coupling optics, which often causes problems such as low uniformity, glaring, and excessive LEDs. Edge-lit LED light guides in automotive applications share a similar principle with the light-guide plates in back-light models of LCD but with much more complicated geometry. However, related literature on the optical design of nonrectangular light-guide plates is very limited. This study addresses the design of planar curved LED end-lit light bars and the optimization scheme for illuminance uniformity. V cuts are used as the optical coupling features, and the lead angles of the v cuts are varied to achieve optimum axial luminous intensity. This study presents a solution to reduce the illuminance difference between the inner and the outer portions of curved light bars by introducing gradual taper v cuts across the curved section. A line graph with preselected anchor points is proposed to define the size distribution of evenly spaced v cuts along the light bar. A fuzzy optimization scheme is then applied to iterate the anchor size to achieve illuminance uniformity. The designs of a planar curve light bar with a rectangular cross section and a light-guide ring with a circular cross section are presented to illustrate the design scheme.
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OBJECTIVE: To establish a high-sensitivity, high-specificity and low-cost hydrogel chip platform for the clinical screening of Y chromosome microdeletions. METHODS: Site-specific extended primers with a common sequence at the 5' end were used for hybridizing with the target. The Cy5-dUTP was incorporated into the products by primer extension, and the products were labeled with fluorescence. Then the extended products were added to the chip for hybridizing with acrylamide-modified common probes immobilized on the chip. After removal of the free Cy5-dUTP by electrophoresis, the signals were obtained by fluorescence scanning. And the detecting conditions of this method were optimized. RESULTS: SY254 of 9 samples was successfully detected with the hydrogel chip. The results showed that 3 were normal and the other 6 with microdeletions (1 female sample as a negative control), which coincided with the results of conventional multiplex PCR-electrophoresis. CONCLUSION: The hydrogel chip platform we established has provided a new technique for the detection of Y chromosome microdeletions, and is beneficial to the diagnosis and treatment of male infertility.
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Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/genética , Carbocianinas , Deleción Cromosómica , Cromosomas Humanos Y/genética , Nucleótidos de Desoxiuracil , Humanos , Hidrogeles , Infertilidad Masculina , Masculino , Aberraciones Cromosómicas Sexuales , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/diagnósticoRESUMEN
OBJECTIVE: To establish a method to detect Down's syndrome through quantitative pyrosequencing of the heterozygous single nucleotide polymorphisms (SNPs) on the chromosome 21. METHODS: An improved allele-specific-amplification was used to screen heterozygous SNPs on the chromosome 21 from 84 normal samples. Pyrosequencing was used to quantitatively determine the ratio between the two alleles of a heterozygote, and the diagnosis of Down's syndrome was thus carried out based on the ratio. RESULTS: By genotyping 84 genomic DNA samples from normal Chinese population, 6 SNPs with a relatively high level of heterozygosity were screened out. Heterozygote coverage of 92.9% was achieved by using a panel of 6 SNPs on the chromosome 21. Ten clinical samples from Down's syndrome patients were quantitatively determined by pyrosequencing, and 9 samples were accurately diagnosed by comparing the ratio of the two alleles. The pyrosequencing results showed that the ratio of the two alleles were 2:1 or 1:2 for the Down's syndrome patients. CONCLUSION: The method has the advantage of a low cost, simple process, and time-saving operation and could be potentially applicable to the rapid diagnosis of Down's syndrome.
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Cromosomas Humanos Par 21 , Síndrome de Down/diagnóstico , Polimorfismo de Nucleótido Simple/genética , Diagnóstico Prenatal/métodos , Alelos , Pueblo Asiatico/genética , Clonación Molecular , ADN/análisis , Síndrome de Down/genética , Femenino , Pruebas Genéticas , Humanos , Cariotipificación/métodos , Embarazo , Diagnóstico Prenatal/economíaRESUMEN
Effective conversion of solar energy into chemical energy by visible light represents a potential strategy for sustainable development. Among which, photocatalytic hydrogen evolution reaction (HER) with a relatively small activation energy (1.23 eV, around 1000 nm light irradiation) is especially attractive. In this work, well-distributed platinum nanoparticles (Pt-NPs) with a width of about 3 nm have been successfully immobilized into the confined coordination interspaces of 3.7 nm diameter, which are facilitated by early transition metal Hf(iv)-based clusters of a self-sensitized palladium porphyrin metal-organic framework. Under visible light irradiation, the resultant Pt@Pd-PCN-222(Hf) (which is also denoted as Pt@Pd-PMOF-2(Hf)) displays superb photocatalytic activity, achieving an unprecedented maximum H2 evolution rate of 22 674 µmol g-1 h-1 with a turn-over number (TON) of 4131.2 in 32 h and the highest turn-over frequency (TOF) of 482.5 h-1 based on Pt-NPs. This photocatalyst can be recycled and reused for three successive runs without significant loss of catalytic activity. This effective strategy takes advantage of the synergetic effect between Pd-porphyrin photosensitizers and Pt-NP co-catalysts confined within nanoscale coordination interspaces incorporating hydrophilic Hf(iv)-oxo clusters.
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Purpose: In order to classify different types of health data collected in clinical practice of hernia surgery more effectively and improve the classification performance of support vector machine (SVM). Methods: A prospective randomized study was conducted. Sixty patients undergoing hernia repair under general anesthesia were randomly divided into two groups, PLMA group (n = 30) and ETT group (n = 30), for airway management. Heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, respiratory parameters and the incidence of complications related to ProSeal laryngeal mask airway (PLMA) and endotracheal tube (ETT) were collected in clinical experiments in order to evaluate the operation condition. On the basis of this experiment, at first, expert credibility is introduced to process the index value; secondly, the classification weight of the index is objectively determined by the information entropy output of the index itself; finally, a comprehensive classification model of support vector machine based on key sample set is proposed and its advantages are evaluated. Result: After classifying the experimental data, we found that SVM can accurately judge the effect of surgery by data. In this experiment, PLMA method is better than ETT method in xenon repair operation. Discussion: SVM has great accuracy and practicability in judging the outcome of xenon repair operation. Conclusion: The proposed index classification weight model can deal with the uncertainties caused by uncertain information and give the confidence of the uncertain information. Compared with the traditional SVM method, the proposed method based on SVM and key sample set greatly reduces the number of samples that misjudge the effect of samples, and improves the practicability of SVM method. It is concluded that PLMA is superior to the ETT technique to hernia surgical. The idea of constructing classification model based on key sample set proposed in this paper can also be used for reference in other data mining methods.
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Máscaras Laríngeas , Catéteres , Herniorrafia , Humanos , Estudios Prospectivos , Máquina de Vectores de SoporteRESUMEN
OBJECTIVE: To investigate the clinical efficacy of Buzhong Yiqi Pill (BYP) combined with imodium in treating post-operational diarrhea in patients undergoing colonic cancer surgery. METHODS: Eighty patients with diarrhea after colorectal cancer surgery were randomized into two groups equally, the control group were treated with imodium (loperamide hydrochloride) and the treatment group treated by BYP combined with imodium. The therapeutic efficacy was analyzed and evaluated comprehensively depending upon a defecation check table developed from the XU Zhong-fa's 5-item 10-integrable system. RESULTS: After treatment, the improvements of the anal controlling capacity, the defecatory sensation, the frequency of defecation in the treatment group were significantly better than those in the control group (P < 0.01 or P < 0.05). The integral function of defecation in the treatment group was obvionsly improved by the end of treatment when compared with before treatment and the control group (P < 0.01). CONCLUSION: The clinical efficacy of the BYP combined with imodium in treating post-operational diarrhea after colorectal cancer surgery were better than that of imodium alone.
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Neoplasias del Colon/cirugía , Diarrea/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Loperamida/administración & dosificación , Complicaciones Posoperatorias/tratamiento farmacológico , Adulto , Anciano , Neoplasias del Colon/fisiopatología , Diarrea/fisiopatología , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Adulto JovenRESUMEN
Chemotherapy resistance has become a major challenge in the clinical treatment of lung cancer which is the leading cancer type for the estimated deaths. Recent studies have shown that nanoparticles as drug carriers can raise intracellular drug concentration by achieving effectively cellular uptake and rapid drug release, and therefore reverse the acquired chemoresistance of tumors. In this context, nanoparticles-based chemotherapy represents a promising strategy for treating malignancies with chemoresistance. In the present study, we developed cationic lipid assisted nanoparticles (CLAN) to deliver polylactide-cisplatin prodrugs to drug resistant lung cancer cells. The nanoparticles were formulated through self-assembly of a biodegradable poly(ethylene glycol)-block-poly(lactide) (PEG-PLA), a hydrophobic polylactide-cisplatin prodrug, and a cationic lipid. The cationic nanoparticles were proven to significantly improve cell uptake of cisplatin, leading to an increased DNA-Pt adduct and significantly promoted DNA damage in vitro. Moreover, our study reveals that cationic nanoparticles, although are slightly inferior in blood circulation and tumor accumulation, are more effective in blood vessel extravasation. The CLANs ultimately enhances the cellular drug availability and leads to the reversal of cisplatin resistance.
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Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Lípidos/química , Nanopartículas/química , Profármacos/farmacología , Células A549 , Animales , Cationes , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cisplatino/química , Cisplatino/farmacocinética , Ácidos Grasos Monoinsaturados/química , Femenino , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/ultraestructura , Poliésteres/química , Polietilenglicoles/química , Profármacos/química , Profármacos/farmacocinética , Compuestos de Amonio Cuaternario/química , Distribución Tisular/efectos de los fármacosRESUMEN
AIM: To investigate the role and potential mechanisms of bone marrow mesenchymal stem cells (MSCs) in severe acute peritonitis (SAP). METHODS: Pancreatic acinar cells from Sprague Dawley rats were randomly divided into three groups: non-sodium deoxycholate (SDOC) group (non-SODC group), SDOC group, and a MSCs intervention group (i.e., a co-culture system of MSCs and pancreatic acinar cells + SDOC). The cell survival rate, the concentration of malonaldehyde (MDA), the density of superoxide dismutase (SOD), serum amylase (AMS) secretion rate and lactate dehydrogenase (LDH) leakage rate were detected at various time points. In a separate study, Sprague Dawley rats were randomly divided into either an SAP group or an SAP + MSCs group. Serum AMS, MDA and SOD, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α levels, intestinal mucosa injury scores and proliferating cells of small intestinal mucosa were measured at various time points after injecting either MSCs or saline into rats. In both studies, the protective effect of MSCs was evaluated. RESULTS: In vitro, The cell survival rate of pancreatic acinar cells and the density of SOD were significantly reduced, and the concentration of MDA, AMS secretion rate and LDH leakage rate were significantly increased in the SDOC group compared with the MSCs intervention group and the Non-SDOC group at each time point. In vivo, Serum AMS, IL-6, TNF-α and MAD level in the SAP + MSCs group were lower than the SAP group; however serum IL-10 level was higher than the SAP group. Serum SOD level was higher than the SAP group at each time point, whereas a significant between-group difference in SOD level was only noted after 24 h. Intestinal mucosa injury scores was significantly reduced and the proliferating cells of small intestinal mucosa became obvious after injecting MSCs. CONCLUSION: MSCs can effectively relieve injury to pancreatic acinar cells and small intestinal epithelium, promote the proliferation of enteric epithelium and repair of the mucosa, attenuate systemic inflammation in rats with SAP.